IMPORTANT study is a multicenter, open-label, prospective, randomized-controlled, non-inferiority trial with a pragmatic approach involving older patients (≥ 70 years old) with advanced hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer, not amenable for curative treatment and without prior therapy for advanced disease, who are suitable to receive CDK 4/6-inhibitors plus endocrine therapy as first line therapy. The study implements two approaches with high level of evidence, namely the use of comprehensive geriatric assessment (CGA) approach in treatment decision making and the use of CDK 4/6-inhibitors as the initial treatment of choice, to investigate whether a common clinical practice (starting dose reduction of CDK 4/6-inhibitors in older patients) with evidence of low certainty can be standardized using a more individualized-based approach. On the basis of baseline CGA assessment, patients will either receive full dose of CDK 4/6-inhibitors plus endocrine therapy (if patients are fit according to CGA) or be randomized to full dose vs. reduced initial dose of CDK 4/6-inhibitors (if vulnerable or frail according to CGA). The study hypothesis is that adjusting the dose according to vulnerability will allow patients to tolerate treatment better without jeopardizing the treatment efficacy. This project has received funding from the European Union's HORIZON 2022 research and innovation actions supporting the implementation of the Mission on Cancer under grant agreement No 101104589.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
495
Either Palbociclib, Ribociclib or Abemaciclib
Either Letrozole, Anastrozole, Exemestane or Fulvestrant in combination with CDK 4/6-inhibitor
Department of Oncology, Helsinki University Hospital Comprehensive Cancer Center and University of Helsinki
Helsinki, Finland
RECRUITINGFourth Oncology Department & Comprehensive Clinical Trials Center, Metropolitan Hospital
Athens, Greece
NOT_YET_RECRUITINGSecond Department of Medical Oncology, Hygeia Hospital
Athens, Greece
NOT_YET_RECRUITINGDivision of Oncology, Department of Medicine, University Hospital, University of Patras Medical School
Pátrai, Greece
NOT_YET_RECRUITINGMedical Oncology Unit, S. Andrew Hospital
Pátrai, Greece
NOT_YET_RECRUITINGSecond Department of Medical Oncology, Euromedica General Clinic
Thessaloniki, Greece
NOT_YET_RECRUITINGRadiation Oncology Unit - Oncology Department, Azienda Ospedaliero Universitaria Careggi
Florence, Italy
NOT_YET_RECRUITING"Sandro Pitigliani" Department of Medical Oncology, Hospital of Prato
Prato, Italy
NOT_YET_RECRUITINGDepartment of Oncology, Akershus University Hospital (AHUS)
Oslo, Norway
NOT_YET_RECRUITINGDepartment of Medical Oncology, Hospital Clinic of Barcelona
Barcelona, Spain
NOT_YET_RECRUITING...and 2 more locations
Time to treatment failure
The time from randomization to treatment discontinuation because of any reason including disease progression, treatment toxicity, or death due to any cause.
Time frame: Up to 5 years from treatment initiation
Overall treatment utility (OTU)
A composite endpoint that will be assessed at the first efficacy evaluation. OTU incorporates objective and participant-reported outcome measures of anticancer efficacy, tolerability and acceptability of treatment providing a simple "good, intermediate or poor" categorization of outcome.
Time frame: Three months after treatment initiation
Overall survival
The time from randomization to death from any cause.
Time frame: Up to 5 years from treatment initiation
Progression free survival
The time from randomization to first documented evidence of disease progression or death from any cause.
Time frame: Up to 5 years from treatment initiation
Time to chemotherapy initiation
The time from randomization until the initiation of chemotherapy at any treatment line after CDK 4/6-inhibitors.
Time frame: Up to 5 years from treatment initiation
Frequency of adverse events
Adverse events will be assessed based on adverse events, as graded by CTCAE v 5.0 before each cycle and up to 28 days after the end of CDK 4/6-inhibitors.
Time frame: Up to 5 years from treatment initiation
Assessment of Quality of life
Quality of life will be assessed using three validated questionnaires, EORTC Quality of Life Questionnaire (QLQ)-C30, Elderly (ELD)-14, and European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L).
Time frame: Until disease progression, participant / physician decision to stop, death, or up to 24 months from treatment initiation whichever occurs first
Time until Quality of life deterioration
QoL deterioration, defined as the time from randomization until any clinically meaningful worsening (using minimal important differences as cut-off) of any QoL aspect measured by the questionnaires.
Time frame: Until disease progression, participant / physician decision to stop, death, or up to 24 months from treatment initiation whichever occurs first
Cost effectiveness
Resource use, length of life and quality of life data will be collected during the trial for the purpose of conducting an economic evaluation.
Time frame: Up to 24 months from treatment initiation
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